title: Contractions induced by NO synthase inhibition in isolated rat basilar artery: role of the endothelium and endogenous vasoconstrictors.
abstract: Alterations of the endothelium may play a role in the generation of cerebral vasospasm. The objective of this study was to investigate the involvement of the endothelium and of endogenous endothelin (ET) on the NG-nitro-L-arginine (L-NOARG)-induced contractions in isolated rat basilar arteries. L-NOARG, NG-nitro-L-arginine methyl esther, and methylene blue, but not D-NOARG, induced concentration-dependent contractions and spontaneous vasomotion. The effect of L-NOARG was reversed by L-arginine and submaximally reduced in de-endothelialized arteries. The contractile effect of L-NOARG was completely suppressed by the ET-antagonists BQ 123 and Ro 46-2005 in a part of the basilar arteries. After washout of the respective antagonist, the L-NOARG-induced contraction started, but was not influenced by a second application of the antagonist. In another part of preparations the antagonists failed to influence the L-NOARG-induced contraction. Inconsistent suppressor effects were also observed after preincubation with ketanserin, Manning compound, losartan, or indomethacin. None of these antagonists reversed the established L-NOARG-induced contraction. Thus, endothelium-derived NO suppresses spontaneous contraction and vasomotion in rat basilar arteries. Endogenous ET, 5-HT, vasopressin, angiotensin or cyclooxygenase metabolites do not cause the contraction induced by inhibition of the NO synthase, but may act as 'trigger factors', that may play a role in rat models of cerebral vasospasm or infarction.
authors.affiliation: Department of Neurosurgery, University of Kiel, Germany.
authors.forename: R G
authors.initials: RG
authors.lastname: Hempelmann
authors.forename: R H
authors.initials: RH
authors.lastname: Pradel
authors.forename: H M
authors.initials: HM
authors.lastname: Mehdorn
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D016232:Endothelins; D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D018721:Muscarinic Agonists; D010456:Peptides, Cyclic; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D019335:Nitroarginine; D012701:Serotonin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D002217:Carbachol; D007650:Ketanserin; D019001:Nitric Oxide Synthase; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D009638:Norepinephrine; D007213:Indomethacin